WARNING: RISKS OF LIVER INJURY and TERATOGENICITY
Because of the risk of liver injury and birth defects, Tracleer is available only through a special restricted distribution program called the Tracleer Access Program (T.A.P.), by calling 1 866 228 3546. Only prescribers and pharmacies registered with T.A.P. may prescribe and distribute Tracleer. In addition, Tracleer may be dispensed only to patients who are enrolled in and meet all conditions of T.A.P. [see Warnings and Precautions].
Liver Injury
In clinical studies, Tracleer caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious liver injury, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration, Warnings and Precautions]. In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with Tracleer in patients with multiple co-morbidities and drug therapies. There have also been reports of liver failure. The contribution of Tracleer in these cases could not be excluded.
In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of Tracleer. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping Tracleer with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction [see Dosage and Administration].
Elevations in aminotransferases require close attention [see Dosage and Administration]. Tracleer should generally be avoided in patients with elevated aminotransferases (> 3 — ULN) at baseline because monitoring liver injury may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 — ULN, treatment with Tracleer should be stopped. There is no experience with the re-introduction of Tracleer in these circumstances.
Teratogenicity
Tracleer is likely to cause major birth defects if used by pregnant females based on animal data [see Contraindications]. Therefore, pregnancy must be excluded before the start of treatment with Tracleer. Throughout treatment and for one month after stopping Tracleer, females of childbearing potential must use two reliable methods of contraception unless the patient has a tubal sterilization or Copper T 380A IUD or LNg 20 IUS inserted, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving Tracleer [see Drug Interactions]. Monthly pregnancy tests should be obtained.
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TRACLEER SUMMARY
Bosentan is the first of a new drug class, an endothelin receptor antagonist.
TRACLEER® is indicated for the treatment of pulmonary arterial hypertension in patients with WHO Class III or IV symptoms, to improve exercise ability and decrease the rate of clinical worsening (see Clinical Studies).
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NEWS HIGHLIGHTSMedia Articles Related to Tracleer (Bosentan)
ED Drug Improves Heart's Pumping Action In Young Patients With Single-Ventricle Disease
Source: Cardiovascular / Cardiology News From Medical News Today [2009.11.19]
Heart function significantly improved in children and young adults with single-ventricle congenital heart disease who have had the Fontan operation following treatment with sildenafil, a drug used to treat erectile dysfunction and pulmonary hypertension, say researchers from The Children's Hospital of Philadelphia. Single-ventricle defects are a collection of cardiac malformations that impair the heart's ability to pump blood.
Published Studies Related to Tracleer (Bosentan)
Bosentan decreases pulmonary vascular resistance and improves exercise capacity in acute hypoxia. [2009.05]
BACKGROUND: Altitude exposure is associated with mild pulmonary hypertension and decreased exercise capacity. We tested the hypothesis that pulmonary vascular resistance (PVR) contributes to decreased exercise capacity in hypoxic healthy subjects... CONCLUSIONS: We conclude that hypoxic pulmonary hypertension partially limits exercise capacity in healthy subjects, and that bosentan therapy can prevent it.
Prophylactic bosentan does not improve exercise capacity or lower pulmonary artery systolic pressure at high altitude. [2009.02.28]
Hypoxic pulmonary vasoconstriction in response to high altitude ascent may contribute to decreased exercise capacity. Endothelin receptor antagonists reduce pulmonary artery pressure and improve exercise capacity in patients with pulmonary arterial hypertension, but their effects on exercise capacity at altitude are unknown.
Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease. [2009.02]
BACKGROUND: Pulmonary hypertension (PH) in chronic obstructive pulmonary disease [COPD] is mainly determined by hypoxemia under respiratory failure by means of the functional hypoxemic vasoconstrictor response. Organic changes of vessels, pulmonary vascular remodelling, is gaining increasing relevance. An imbalance of endothelial products takes place with overload of vasoconstrictors and thrombogenic autacoids over vasodilators and anticoagulant factors. Among vasoconstrictors, endothelin is claimed to be an important factor. Our aim is to assess the effect of the anti-endothelin drug Bosentan on pulmonary hemodynamics and lung function in patients affected by COPD and PH... CONCLUSION: This preliminary report suggests that the use of Bosentan in the treatment of PH in COPD is beneficial.
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient. [2009]
Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcomes. Bosentan is an oral endothelin-1 receptor antagonist (ERA) that has been shown in a large randomized placebo-controlled trial (BREATHE-1) to be effective at improving exercise tolerance in patients with PAH in functional class III and IV...
Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. [2008.12.16]
OBJECTIVES: Our goal was to investigate the effect of treatment with the oral dual endothelin receptor antagonist bosentan on the hemodynamics and exercise capacity of patients with chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND: CTEPH is characterized by vascular obstruction and remodeling, leading to increased pulmonary vascular resistance (PVR). Although pulmonary endarterectomy (PEA) is potentially curative, medical therapy is needed in patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA... CONCLUSIONS: This study demonstrated a positive TE of bosentan on hemodynamics in this patient population. No improvement was observed in exercise capacity. Further trials are needed to define the role of medical therapy in patients with CTEPH (Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension; NCT00313222).
Clinical Trials Related to Tracleer (Bosentan)
BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology [Completed]
This 6-month open label study will evaluate the long term safety of bosentan (via oxygen
saturation) and efficacy (exercise capacity) in patients who have completed the BREATHE-5
study (PAH related to Eisenmenger physiology). Treatment duration is 6 months.
Effects of Tracleer (Bosentan) on Pulmonary Arterial Hypertension Related to Eisenmenger Physiology [Completed]
This study evaluates the effects of bosentan on oxygen saturation, hemodynamics and exercise
capacity in patients with pulmonary arterial hypertension related to Eisenmenger physiology.
Patients receive bosentan or placebo for 16 weeks.
The Effect of Tracleer® on Male Fertility [Completed]
The objective of the study is to evaluate the effects of chronic TRACLEER® treatment on
testicular function via semen analysis in male patients with primary pulmonary arterial
hypertension (PAH).
Effect of Bosentan on Skin Fibrosis in Patients With Systemic Sclerosis [Completed]
Endothelin-1 is a potent vasoconstrictor and binds to two receptors, ET-A and ET-B, which are
variable expressed on endothelial cells, smooth muscle cells, and fibroblasts. Furthermore,
endothelin-1 has been found to be released in vitro by scleroderma fibroblasts and could
contribute to the development of dermal fibrosis in systemic sclerosis. Bosentan is a dual
receptor antagonist, that competes with the binding of endothelin-1 to both receptors and has
already been approved for the treatment of pulmonary arterial hypertension in Europe, the US,
and some other countries. The purpose of this study is to evaluate the effect of bosentan
treatment on skin fibrosis and functionality in patients with systemic sclerosis.
Open Label Extension Study in Patients With Idiopathic Pulmonary Fibrosis Who Completed Protocol AC-052-321/ BUILD 3 [Enrolling by invitation]
This Open-label extension study in patients with Idiopathic Pulmonary Fibrosis who completed
protocol AC-052-321 / BUILD 3 will asses the long term safety and tolerability of bosentan in
patients with idiopathic pulmonary fibrosis (IPF).
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Page last updated: 2009-11-19
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